Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in ....Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in doing so, will provide significant benefit by revealing the potential for iPSC to be used for functional translation of human genomics.Read moreRead less
How neurons maintain their fate. This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintenance is essential because when it fails, cells lose their ability to perform their ascribed function, which impedes organism fitness. This project aims to define how two proteins work in partnership to maintain the identity of brain neurons. We intend our discoveries to stimulate new research, for example to test whether the h ....How neurons maintain their fate. This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintenance is essential because when it fails, cells lose their ability to perform their ascribed function, which impedes organism fitness. This project aims to define how two proteins work in partnership to maintain the identity of brain neurons. We intend our discoveries to stimulate new research, for example to test whether the human counterparts of the Drosophila proteins studied here, function similarly. Benefits will be provided in the form of job creation, and new knowledge in fundamental aspects of life, including brain development and cell fate maintenance.Read moreRead less
How protein and RNA cargo are sorted into exosomes. This project aims to understand how proteins and RNA are selected for packaging into exosomes and participate in the biological functions mediated by these vesicles. Exosomes are small membranous extracellular vesicles released by cells which contain protein and RNA cargo and are involved in intercellular communication. Determining how the exosome cargo is selected and related to its function in intercellular communication is expected to show h ....How protein and RNA cargo are sorted into exosomes. This project aims to understand how proteins and RNA are selected for packaging into exosomes and participate in the biological functions mediated by these vesicles. Exosomes are small membranous extracellular vesicles released by cells which contain protein and RNA cargo and are involved in intercellular communication. Determining how the exosome cargo is selected and related to its function in intercellular communication is expected to show how these vesicles maintain cellular homeostasis. The findings will expand knowledge in the area of microRNA biology, proteomics and develop expertise in bioinformatics.Read moreRead less
The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained perso ....The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained personnel in genomics and neuroscience. This should deliver many benefits, including a better understanding of how the brain forms, training of higher degree by research students, as well as tools and methods of benefit to the academic research and biotechnology sectors.Read moreRead less
Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water ....Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water and soil should lead to deeper understanding of the dynamics, variation and transfer of genetic material within these resources’ microbial communities, strategies to manage microbial diversity, and improved productivity and long-term sustainability for these resources.Read moreRead less
Discovery of Novel Bacteriophage with the Capacity to Modulate Gut Bacteria. This project aims to experimentally validate the largest ever collection of bacterial viruses (bacteriophages) within the gut microbiome. This project expects to generate new knowledge in the area of bacteriophage biology and genomics by using the innovative approaches of wet-lab and bioinformatic genome analyses. Expect outcomes of this project include the discovery of novel phages using bioinformatics, wet-lab validat ....Discovery of Novel Bacteriophage with the Capacity to Modulate Gut Bacteria. This project aims to experimentally validate the largest ever collection of bacterial viruses (bacteriophages) within the gut microbiome. This project expects to generate new knowledge in the area of bacteriophage biology and genomics by using the innovative approaches of wet-lab and bioinformatic genome analyses. Expect outcomes of this project include the discovery of novel phages using bioinformatics, wet-lab validation of their activity and characterisation of their potential to contribute new bacterial host metabolism. This should provide benefits, such as advancement to our understanding of bacteriophages, improved bioinformatic software, and a characterised collection of commercially valuable bacterial strains and phages.Read moreRead less
A cellular hub for the organisation of T cell priming. This project aims to delineate the cellular interactions involved in the initiation of immune responses by utilising advanced in vivo imaging. Adaptive immunity in vertebrates functions via the acquisition of signals by immune cells via complex interactions with other immune cells, yet these exchanges are difficult to observe and define. This project expects to provide insights into the mechanisms that underpin effective cell-mediated immune ....A cellular hub for the organisation of T cell priming. This project aims to delineate the cellular interactions involved in the initiation of immune responses by utilising advanced in vivo imaging. Adaptive immunity in vertebrates functions via the acquisition of signals by immune cells via complex interactions with other immune cells, yet these exchanges are difficult to observe and define. This project expects to provide insights into the mechanisms that underpin effective cell-mediated immune responses. The expected outcomes are to generate fundamental new knowledge about immune responses and enhance capacity to study the immune system. This could benefit future development of new vaccines and therapies to improve health.Read moreRead less
Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioi ....Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioinformatics to dissect the functions of the lymphoid stromal cells and their roles in the swelling of lymphoid tissues during immune responses. This will provide vital information about the biology of these understudied cells and reveal the ways in which they support the generation of immunity.Read moreRead less
Diet influences the selective advantage of mitochondrial DNA mutations. This project aims to examine critical mechanisms that affect mitochondrial DNA variation within species. It aims to test the hypothesis that mitochondrial DNA haplotypes have the potential to be under nutritionally induced balancing selection as a consequence of cellular signalling and/or Adenosine triphosphate (ATP) production by mitochondria. Diet can vary both seasonally and geographically and is a key environmental param ....Diet influences the selective advantage of mitochondrial DNA mutations. This project aims to examine critical mechanisms that affect mitochondrial DNA variation within species. It aims to test the hypothesis that mitochondrial DNA haplotypes have the potential to be under nutritionally induced balancing selection as a consequence of cellular signalling and/or Adenosine triphosphate (ATP) production by mitochondria. Diet can vary both seasonally and geographically and is a key environmental parameter that influences the ability of a species to colonise new habitats. The project plans to characterise the functional links between specific mitochondrial DNA haplotypes, mitochondrial functions and organismal traits. The expected outcome is a more precise grasp of the processes influencing genetic variation within and among species, which would inform current issues in ecology and genetics.Read moreRead less
Radical change in the architecture of a nucleus: loss of typical DNA organisation systems in dinoflagellates. The genetic blueprint of all higher cells is stored in the cell nucleus, and proteins called histones provide the filing system for compactly stacking and organising the cell's DNA. One group of organisms, the dinoflagellate algae, have lost this histone system. This project will provide insight into their alternative DNA management systems.